DBT to formulate guideline on HIV vaccine trials

Jayashree Padmini - New Delhi

Recognizing the need for defining a clear-cut strategy on acceptability levels to address ethical concerns, the Department of Biotechnology (DBT) is in the process of formulating a roadmap for clinical trials of HIV vaccine in the country.

The department, keeping the existing guidelines of WHO and UNAID as referral documents and in consultation with institutions like ICMR, is actively working on drawing up a unified blueprint that will define the parameters of research on a DNA vaccine for HIV from the stage of candidate selection, to pre clinical and clinical trial phases I, II & III. Dr Vinayak, Adviser, DBT, informed Express Pharma Pulse that this exercise has been going on for the last one year and all minutiae except that on the clinical trial part have been fine tuned.

''We are still debating on the ethical issues involved in vaccine trials as it can create the same immune response as that of virus infection. We are evaluating the global experience and are in the process of developing essential guidelines to be put in place in the country,'' he added. Other challenge the department has to tackle will be to outline the parameters for preparing trial sites.The HIV vaccine developed under the Indo-US vaccine programme of DBT is now in the preclinical stage where it has completed mice studies and embarked on study on primates that is expected to take a minimum of nine months. In order to reduce the time span involved, the preclinical toxicology studies are being undertaken simultaneously, informed Dr Vinayak.

At global level there is no ideal experimental model and under the Indo-US programme the first of its kind model of SHIV (Simian Human Immuno Virus) is developed. The department is looking at technology collaborations with Indian and overseas pharma majors with an eye to bring in expertise in novel delivery mechanisms, adjuvant, unique technologies that will give better immune response, etc., in a bid optimize the efficacy and cut down time period.

DBT is working towards developing a Subtype C specific vaccine and to subsequently develop a cocktail vaccine to address all genotypes occurring in the country. In its vaccine development initiative, the department has taken a prime boost approach of priming with DNA and boosting with protein. The institutes involved in the project are NARI Pune, CMC Vellore, AIIMS New Delhi, PGI Chandigarh, NICED Calcutta.
The multi centric project on HIV started five years back with a focus on the Indian strain has analyzed 700 odd isolates from across the country, using HMA technology. The study revealed that 75 per cent of the HIV in circulation is sub type C wherein 85 per cent is the C2 variety and the remaining 25 per cent constitutes Sub types A, B, E and recombinant forms.

Dr Vinayak says that with the naturally occurring genetic manipulation there is the possibility of more recombinant forms coming in enhancing the need for developing a cocktail vaccine. Stress is also given on generating the immune response data, viz., CTL response and neutralizing antibodies that would act as a good marker to evaluate the candidate vaccine. The major challenge for the programme is in the code-on optimization to achieve right response and the high cost involved is a prohibitive factor.